Bepler G, Jaques G, Havemann K, Koehler A, Johnson B E, Gazdar A F
Cancer Res. 1987 Apr 1;47(7):1883-91.
Two small cell lung cancer (SCLC) cell lines were established from pericardial and pleural effusions of a patient with histopathologically proven SCLC of the oat cell type. Chemotherapy was administered without response during the 148-day period prior to the establishment of the first cell line, SCLC-22H, and some of the same drugs were administered in the 15 days prior to the establishment of the second cell line, SCLC-21H. Both cell lines differed markedly in their biochemical, kinetic, and morphological properties. Although the biomarkers L-Dopa decarboxylase, bombesin, carcinoembryonic antigen, and neurotensin were detectable in SCLC-22H, they were undetectable or low in SCLC-21H. The population doubling time was twice as fast and the colony forming efficiency higher in SCLC-21H than in SCLC-22H. They both expressed high concentrations of the SCLC marker enzymes neuron-specific enolase and the creatine kinase isoenzyme BB and showed no significant differences in their chromosomal characteristics. c-myc was amplified and expressed in both cell lines, and SCLC-21H had an additional rearranged and amplified EcoRI c-myc fragment. Morphological differences were apparent in liquid culture, cytology, and xenograft histology; SCLC-21H grew much more loosely than SCLC-22H, and had more prominent nucleoli and more abundant cytoplasm. Ultrastructurally dense core granules were present in both cell lines. SCLC-21H thus expressed properties of the variant cell type of SCLC, whereas SCLC-22H had mixed classic/variant features. An in vivo progression of the patient's tumor from a pure small cell to a mixed small cell/large cell morphology could be demonstrated, which suggests that cell line SCLC-22H represents a cell type characteristic for the transitional phase of the tumor. The features of this cell line therefore define a new subclass of SCLC called transitional cell type. SCLC-22H may be of use to study the mechanisms involved in the classic to variant transition, which probably has a considerable impact on the prognosis and response to therapy.
从一名经组织病理学证实为燕麦细胞型小细胞肺癌（SCLC）患者的心包积液和胸腔积液中建立了两株SCLC细胞系。在建立第一株细胞系SCLC - 22H之前的148天期间进行了化疗，但无反应，且在建立第二株细胞系SCLC - 21H之前的15天内使用了一些相同的药物。两株细胞系在生化、动力学和形态学特性上有显著差异。尽管在SCLC - 22H中可检测到生物标志物L - 多巴脱羧酶、蛙皮素、癌胚抗原和神经降压素，但在SCLC - 21H中未检测到或含量很低。SCLC - 21H的群体倍增时间比SCLC - 22H快两倍，集落形成效率也更高。它们都高表达SCLC标志物酶神经元特异性烯醇化酶和肌酸激酶同工酶BB，并且在染色体特征上没有显著差异。c - myc在两株细胞系中均有扩增和表达，且SCLC - 21H有一个额外的重排和扩增的EcoRI c - myc片段。在液体培养、细胞学和异种移植组织学中形态学差异明显；SCLC - 21H生长比SCLC - 22H松散得多，核仁更明显，细胞质更丰富。超微结构上两株细胞系均存在致密核心颗粒。因此，SCLC - 21H表现出SCLC变异细胞类型的特性，而SCLC - 22H具有经典/变异混合特征。可以证明患者肿瘤在体内从纯小细胞形态进展为混合小细胞/大细胞形态，这表明细胞系SCLC - 22H代表肿瘤过渡阶段的一种细胞类型特征。因此，该细胞系的特征定义了一种新的SCLC亚类，称为过渡细胞类型。SCLC - 22H可能有助于研究经典向变异转变所涉及的机制，这可能对预后和治疗反应有相当大的影响。
